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  • mattoddchem 10:31 pm on June 25, 2014 Permalink | Reply  

    Sabbatical Day 1 

    Today I’m starting a 6-month sabbatical. Sabbaticals are a perk of academia (though every profession should have them) allowing the sabbaticalee to learn something new, start up a new project or mull over a large problem, freed of administrative and teaching responsibilities. It also provides time to finish papers, write grant proposals etc. Some people, for pragmatic reasons, take sabbaticals at their home institution, a staybattical if you will, but nothing beats the disruption of a move, and talking to new people, for thinking about tough problems in a new way.

    So what am I doing? I’m in Boston till September then in Oxford till January.

    The focus is on open source drug discovery. My lab ran an open science project in drug synthesis in tropical diseases with WHO, and is now at the centre of a fascinating experiment in open source drug discovery known as Open Source Malaria (OSM), with MMV. The first malaria papers will be written up in the coming months. There is a huge amount to do in OSM, but the project has achieved some key objectives already, in terms of demonstrating how open drug discovery can function efficiently, leveraging the power of a nimble and distributed group and identifying new, potent anti-malarial drug candidates. More on OSM in future posts. One of my main objectives during the sabbatical is to look at how we can scale-up OSM in the next 3 years, since it needs to be made larger if it is to compete effectively with established, large, closed projects operating elsewhere.

    University of Sydney contributors to OSM - me, Tom MacDonald, Jo Ubels and Alice Williamson

    University of Sydney contributors to OSM – me, Tom MacDonald, Jo Ubels and Alice Williamson

    My lab is starting up a project in Open Source Tuberculosis, with GSK Tres Cantos. This is exciting for lots of reasons, and I’ll be writing more on this project soon too, but with TB we move slightly closer to a disease area where drugs have a positive net present value, jargon for the idea that there is a profit incentive to TB drug discovery that makes an open approach more difficult to conceptualize end-to-end: how can an open source approach compete with commercial or academia/industry projects where future profits (guaranteed through patents) are used to off-set up-front funding of the research?

    So here are the two questions I’ll be looking at:

    1) How can we scale-up open source drug discovery precedents like OSM to become part of a new pharma industry?

    2) Could we use open source drug discovery in areas normally associated with a profit, such as cancer, Alzheimer’s or diabetes?

    These are great questions because it’s not clear how to answer them. My expertise is organic chemistry, and that is the important technical discipline I bring to such questions. The experience of previous open science projects has I think taught us a lot about how to run them. But I don’t want to contribute anything to a research effort that is either sub-par, or which is not maximally efficient. I don’t think we’re doing drug discovery (or, indeed, organic chemistry) efficiently. Indeed I think we’re hemorrhaging resources in the way we’re currently doing science. It is, to be frank, toe-curling. So I want to look at the two questions above so that I and my students can contribute only to the very best projects with the best structure and the most likelihood of finding a new medicine.

    To start to answer question 1, I’m helping run this unique meeting. The outcomes will be written up and extensively disseminated. It’s very exciting to get this group of people together, all of whom are in touch with an even wider network of talented people who are interested in trying something new. We’ll be discussing prizes, for example – the idea that if you award large sums for research performed you can separate out the costs of research from the price of a medicine. I’m very excited to see what comes out of the meeting.

    To answer question 2 I am visiting two institutes, both leading the field in data sharing for drug discovery in areas such as epigenetics. So from late June to mid-September I’ll be in Boston working with Brian Hubbard’s team at the Harvard/MIT Broad Institute – this is a great fit because Brian and his colleagues have extensive industry experience, but have moved to the Broad to try out something genuinely new.

    Boston, on the morning of Day 1

    Boston, on the morning of Day 1

    Then from late September to early January I’ll be at the Structural Genomics Consortium at the University of Oxford, working with Chas Bountra. (The chief medicinal chemist there, Paul Brennan, is a buddy of mine from postdoc days at Berkeley). Chas has been a leader in open science for some time, securing extensive funds for the SGC’s activities and working effectively with the pharma industry to share data that underpins much of the structural biology that fuels rational drug design. The aim in both places: to collect together a group of people willing and able to try a project in open source drug discovery in an area such as cancer. i.e. to define a target, a hit compound, a scientific project structure and a governance/financial plan for how something like this might work. Both the Broad and the SGC lead the world in sharing data related to biomedicine, but neither have an open source project currently operating – i.e. one where anyone from outside those institutes may contribute, and it is clear what the project will do tomorrow. Collecting such a group together is really tough, and I don’t know how to do this, which is why I need a sabbatical. The aim is a project that is properly federated – labs in several countries working on the same project, using local funds, acting as a kernel, to which anyone else may contribute should they have the expertise. How?

    So I’m in Boston till September, then Oxford till the end of the year. Ping me if you want to talk about open drug discovery or organic chemistry. Even better, if you’re interested in trying out something in open drug discovery, by contributing to a consortium of loosely affiliated scientists who share what they do each day, please get in touch.

     
  • mattoddchem 2:34 pm on May 13, 2014 Permalink | Reply  

    Open Source Pharma and Prizes 

    I’m involved in a meeting happening next month in Italy that is asking “Can we develop a new open source pharmaceutical industry?” We’ll be talking amongst other things about incentives (such as prizes) and new ideas for the structure of pharma (legal and economic) and trying to come up with some pilot projects. This post serves as an announcement of the meeting and a description of the agenda – true to the philosophy underlying the idea, the agenda is open to input from anyone (please just comment below). This page may therefore change in response to input from people, so any changes will be tracked.

    Context: A while back, when my lab first started working on open source research for neglected tropical diseases, I was contacted by Jaykumar Menon, formerly of the X-Prize and now professor of practice at McGill University. He was interested in whether we’d considered prizes to stimulate activity. This got me to thinking about ways we might be able to combine prizes and completely open ways of working. Jay has now managed to secure funding from the Rockefeller Foundation to host a meeting to start looking at these ideas in detail. It’s taking place at the Rockefeller Bellagio resort on Lake Como, July 2014. Only 23 people can come, and we’re trying to create a diverse mix of attendees from across research, policy and philanthropy. Besides generating the funding and momentum for the meeting, Jay has driven the gathering together of a diverse set of people, and I’ve chipped in where I’m able, since we’ve learned a lot in recent years about how open source drug discovery works as part of Open Source Malaria (including how we’re operating the consortium) and in previous work with WHO on open source drug synthesis. I also gathered a group at WHO last year to ask “Is Open Source Drug Discovery Practical?” and though I’ve not yet uploaded the recordings of the session, and though there are many issues to work through, the answer to that question looked to be “yes”.

    Below is the current status of the blurb about the meeting and a draft agenda, derived from Jay’s original concept note. Please feel free to comment/criticise below. We’d love to hear about anything we might be missing, or relevant literature or people we should be talking to. An objective of the meeting is to discuss but also to create viable project proposals that we could take to possible funders for formal comment.

    On a personal level, despite my finding this general concept immensely exciting, there are so many questions one can ask and discuss specifically on prizes – how would prizes be awarded? For what? Who might fund a prize, and why? How would a prize be governed so that it is compatible with open ways of working? What is the role of the private sector in prize-driven, open projects? How would a prize alter the motivations for people to participate? I’ve also become increasingly interested in an important feature of open source I have noticed over the last two years in operation: an open arena is a way to combine competition and collaboration. I hope we can explore this at the meeting and beyond.

    The purpose of the meeting is to nurture the growing but powerful field of open source pharma. Items for discussion:

    1) What does “open” mean, for example the difference between open source and open innovation? My view on this is that open source means something very specific – that all data and ideas are shared openly, that anyone may participate in a project at any level. Open innovation refers to a competition in which there is no requirement for competitors to share anything. These two approaches are therefore polar opposites in terms of workflow).

    2) The relevance and prospects of open source for pharma, at each stage of the pipeline and including the role of generics manufacture or commercial pharma as partners/contractors.

    3) Open source pharma in the context of other approaches already being discussed or developed, including push mechanisms (traditional grants + Product Development Partnerships) vs pull mechanisms (Advance Market Commitments, priority review vouchers). Also patent pooling. The focus of the meeting needs to be distinguished from other initiatives that are attempting to find new drugs but which are not adopting open models.

    4) A possible global incentive prize for an open source, patent-free drug candidate (initial target: probably TB (the TB bacillus resides in nearly 1/3 of humanity), but the ideas are more generally applicable to e.g. malaria, antibiotics. Open source is a way of doing research, but prizes could incentivise it.

    5) Consider forming a light touch network/consortium for the largely on-line and nationally-based open source pharma communities

    6) Work jointly to draft a project for taking the field forward, to be finalized with inputs from funders in the 4 months post-meeting

    7) Jointly author a paper to be published in a journal on the contours, promise, and a way forward for open source pharma

    Taking these points, we can draft an agenda for the 2.5 days:

    Session 1: Setting the scene- what’s wrong in the kingdom of drug R&D

    • Current needs and gaps
    • Whether and why the current system fails
    • Illustration: peculiarities of TB (possibly also malaria, antibiotics)

    Session 2: Other existing incentives and enabling mechanisms

    • Incentives: Push and pull mechanisms
    • Models: PDPs, pharma spin offs and initiatives (e.g. Lilly Chorus model)
    • Example: Piero Olliaro to speak about current initiatives in TB drug discovery/development. What have they delivered? What are they promising to deliver? Are such initiatives solutions, or partial solutions?

    Session 3: Open source research: what does it really mean?

    • Examples of Open Source (OS) drug dIscovery/development
    • Strengths and weaknesses of OS research
    • Can we develop minimum criteria for what counts as OS?
    • What would OS Pharma look like?

    Session 4: New ideas for incentives & mechanisms

    • Prizes: example of past experiences; proposals that have been made
    • Innovative management of IP: patent pooling to facilitate research (examples from other areas)
    • Combining these ideas (e.g. the MSF 3 P proposal)

    Session 5: Exploring an end to end system based on incentives and enabling mechanisms

    • Can push, pull and pooling work with open source research?
    • What would be the business model? Can this work in TB? can this work beyond TB?
    • Proposal for a light touch consortium
    • Proposal for a draft project

    Status of Invitees
    1. Jaykumar Menon, McGill
    2. Matthew Todd, University of Sydney and Open Source Malaria
    3. Manica Balasegaram, MSF
    4. Els Torreele, OSF
    5. Piero Olliaro, WHO/TDR
    6. Zakir Thomas, OSDD
    7. Tanjore Balganesh, OSDD
    8. UC Jaleel, OSDD
    9. R. Venkat, TATA Trusts, Dorabji Trust
    10. Arun Pandhi, TATA Trusts
    11. Peter Kolb, University of Marburg
    12. John Wilbanks, Sage Bionetworks
    13. Bernard Munos, Innothink/Faster Cures
    14. Tomasz Sablinski, Transparency Life Sciences
    15. Sherwood Neiss, Crowdfund Capital Advisors
    16. John McKew, NIH/NCATS
    17. [MMV]
    18. Melinda Richter, head of Janssen Labs
    19. Samir Brahmachari, Chief Mentor, OSDD
    20. Rob Don, DNDi
    21. [Free]
    22. [Journalist]
    23. Sarah Dennis, McGill University (logistics)

    Collection of Relevant Links/Ideas:
    MSF summary of alternative financing/research models, includes: “When DNDi developed ASAQ in partnership with sanofi-aventis they insisted that the newly developed medicine not be patented. In doing so they have now been able to start work on transferring technology to an additional African industrial partner to produce and sell the medicine.” and “As these prizes only take the research so far, it is important that adequate measures are put in place to make sure that when a final product relying on this innovation is developed, access for the populations in need is secured.

    Impact of patents, and the new Trans Pacific Partnership

    Guardian Global Dev article on advice on how to develop drugs

    Patent Pooling

    CASMI

    The EU PreDiCT-TB Consortium (not open as far as I know).

    The Critical Path to TB Drug Regimens (also not open as far as I know).

    The Stop TB Partnership

    Guardian letter from MSF on “Big Pharma’s Ransom for New Drugs”

    Toll-access review on “Curing TB with Open Science

    Guardian article (9th May 2014) on problem of antibiotic resistance

    Kauffman Foundation report on economic incentives that might help in repurposing efforts by pharma (May 2014)

    The Accelerating Medicines Partnership (relevant to non-infectious diseases)

    WHO/TDR’s ongoing interest in alternative financing mechanisms. May 2014

    DNDi’s views on the advantage of the PDP model. May 2014

    State of play on NCEs for NTDs, with shared data from DNDi. Feb 2014

    (Updated 21/5/14 with input by email from Manica Balasegaram from MSF, including the first draft agenda)

    The Original Concept Note Description:
    TOWARDS A NEW, GLOBAL, OPEN SOURCE PHARMACEUTICAL INDUSTRY, JULY 16-18, 2014. ROCKEFELLER FOUNDATION CENTER, BELLAGIO, ITALY

    Overview: A small gathering of a maximum of 23 people on the shores of Lake Como at the Rockefeller Foundation Center in Bellagio, Italy on July 16-18, 2014, on the subject of open source pharmaceuticals.

    Where: The Rockefeller Bellagio Center is a renowned spectacular site – the former villas of a princess, literally on the shore of Lake Como.

    Rockefeller Bellagio Center

    Who: A diverse and meaningful set of parties. Convening organizations include the Rockefeller Foundation, the Open Society (Soros) Foundations, and McGill University. Other attendees include representatives from the Tata Trusts (India’s largest philanthropic organization), the World Health Organization, Cipla (the global pharmaceutical manufacturer and generics giant), Medicins Sans Frontieres (Doctors Without Borders), Open Source Malaria, OSDD (the Open Source Drug Discovery initiative, an India-based consortium of 50+ universities, software giant Infosys, and the national supercomputer system of India; OSDD has already sequenced for the first time the TB genome), private sector entrepreneurs, and a crowdfunding pioneer.

    When: The meeting is Wednesday through Friday, July 16-18, 2014; participants are encouraged to attend all three days. Most participants will arrive the evening of Tuesday July 15, and leave Saturday morning, July 19.

    Logistics: Milan airports (LIN or MXP) are closest. Local transportation, food (all meals), and lodging (in the villas) will be provided.

    What’s It All About: Truly radical innovation to meet health needs. An inspiration: “Linux for drugs.” Specifically, a move away from closed-door, market based systems, towards an open source (meaning crowdsourced, and patent free) pharmaceutical industry, an emerging avenue drawing from extreme advances in computational technologies, collaborative methodologies, and Linux-type approaches to IP.

    The need of course is dire. Despite the efforts of the philanthropic, government, and private sectors, the health needs of billions globally are still going unmet, and research is still incommensurate with the scale of the problem. For example, only 1% of new approved drugs are for diseases of the developing world. And in high income countries, research into high impact but low-revenue drug classes such as antibiotics is too sparse, and overall drug development costs are extremely high, resulting in a lack of affordability. A variety of alternative approaches exist – we will focus here on the emerging open source movement. Imagine a new crowdsourced patent free drug candidates, going through publicly funded preclinical and clinical trials (funding interest has already been expressed), then being taken up by generics manufacturers on a market basis to create affordable cures for billions. Questions: How real is open source pharma? What are its prospects? And what is the path forward?

     
  • mattoddchem 12:24 pm on July 15, 2013 Permalink | Reply
    Tags: Collaboration, Malaria, , Open Source Drug Discovery, Open Source Research   

    An Example of Open Source Drug Discovery 

    “Open Source Drug Discovery? How does that work?” I am asked this quite a lot. There are some principles and core practices that are involved, embodied in the Six Laws, but those are quite hifalutin. Let me give a practical example.

    The main point is that everything is open, so anyone can come along, make molecules, do biology, do informatics, contribute data to the lab notebooks, coordinate the research and generally contribute in any number of ways for which there are simple technological solutions. All sorts of inputs are possible, including experimental ones.

    Earlier this year there was a need to make a bunch of molecules as part of the first medicinal chemistry campaign in the open source malaria project. The hit molecule that was the starting point had an ester in it, and initial results had shown that the ester was a problem. There were several ester replacements that needed to be synthesized. Many of these had been made. A few had either not been tackled or were proving difficult to make. Alice Williamson made up a “Wanted” poster to highlight that anyone could have a go at making them (see below, and in these nice images of the process of collaboration that Alice also made).

     

     

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    Because these difficulties were being tackled in real time, other scientists could read about them and suggest solutions. Patrick Thomson, an Edinburgh PhD student, was reading this and decided to join in. He got going in the lab on the sulfonamide sE, started posting his data to the same lab notebook the Sydney team were using (to make it easier to compare and share data) and started his own blog to help marshall and summarize results. He corresponded with a student in my lab in Sydney to overcome synthetic hurdles. Several of us worked together to ensure quality control of the data – simple in the digital age.

     

    Image
    And Patrick nailed it. He made the compound. He then mailed it off for biological evaluation. Not to Sydney, which would be a waste of good funds for freight charges, but to a local lab at The University of Dundee. With the appropriate controls and sharing of all data, testing of compounds in different labs can be trusted to deliver a consistent picture.

     

    Image
    In the event, Patrick’s molecules (he tested 3) were inactive. This is a shame, but at the same time the ester/sulfonamide replacement is an obvious one to make and the data enhance the paper where these results will go, on which Patrick will be an author.

    Patrick showed great initiative here, and philosophical agility – he got involved with something unfamiliar where he had not met the people he’d be working with. Maybe it’s because he agreed with the principles of openness, or maybe it was because he saw that all project data were being shared so trust wasn’t an issue – he could see the project involved quality science. Either way, Patrick has provided an excellent example of how open source experimental lab-based research can work on a practical level.

    Which makes one think of all sorts of added benefits of working in a genuinely open manner. One is that open source research provides a low-tech infrastructure for researchers from developing (endemic) countries to get involved in collaborative projects with their peers in the developed world. There are no expensive online tools, no subscription fees for software. Researchers carry out their work in local labs, and share all the data online using existing technology solutions. Crucially the mechanism scales because researchers interact directly, rather than having to pass everything by a bottleneck professor. There is no monolithic “aid” program needed, just the means for people to work together effectively and efficiently. The involvement of endemic labs remains to my mind a top priority target for open research – the barrier is identifying the labs with the right level of chemical facilities (if anyone has any ideas…).

    Today the Open Source Malaria landing page is launched – the project used to be called Open Source Drug Discovery for Malaria, but the name was changed partly to highlight more the real essence of the project – open source. Much of the research is about basic synthetic chemistry, or biology and yes it’s aimed at finding new medicines for malaria, but at the same time the power of the approach lies in how it changes the way we do basic science. The new website highlights the most productive tools used thus far – the lab notebooks, the Github To Do list, the Twitter account, the wiki.

     

    Image

     

    With these simple tools, Patrick was able to make an important, material contribution to an experimental research project without ever leaving his Wimbledon-winning home country. Anyone else can do the same if the inviolable principles of open source are agreed upon – No Need to Ask.

     

     
  • mattoddchem 10:50 pm on June 7, 2013 Permalink | Reply  

    Open Source Competitions and Prizes #1 

    I recently read Future Perfect by Steven Johnson. The book articulates what is meant by a person being a “Peer Progressive” – someone with a set of values based on the power of distributed networks to solve problems (a “Baran Web”) as opposed to a more regulated, centralized mechanism (a “Legrand Star”). It’s an interesting read that gets better as the book progresses. Lots of stories, but there is one particular gem.

    There has been recent talk about prizes being used to alter the way drugs are found, such as Bernie Sanders‘ proposals for ways of funding the prize pot. I’ve written before about the idea of a teamless competition for open projects. We planned this, but have not yet deployed it – more about that later.

    What I find interesting is Johnson’s description of the use of prizes (“premiums”) in mid-18th century England to find a way to produce a deep “Turkey Red” dye derived from madder plants. The organization administering this prize, and others, would become the Royal Society of Arts (RSA); the competitions were very successful. The thing that struck me most about the story was the mechanism of promoting innovation – no patents in a competition with a significant prize where the aim is something of commercial significance. As Johnson quotes from the Rules and Orders published by the Society in 1765: “No person will be admitted a candidate for any premium offered by the Society who has obtained a patent for the exclusive right of making or performing anything for which such premium is offered.” As Johnson says “Prohibiting patents meant that solutions could circulate more quickly through society, and could be easily improved upon by subsequent inventors or scientists. The RSA wanted you to profit from your idea. They just didn’t want you to own it.”

    This, to me, is a crucial aspect of whether patents are harmful for drug discovery or whether they promote innovation. This also goes to the heart of how to run prizes for drug discovery. If we want the best ideas and for those to flow freely, we shouldn’t have a secretive research process. Jamie Love’s suggestion was to de-link the research process and the process of reclaiming costs. The deal is: make me a drug for cancer and I will give you a billion dollars, but you don’t have any say in how much the medicine will cost. Will that work? I don’t know, but it’s a possible solution that would allow the free sharing of information during the discovery process, which is why it’s interesting. I predict in the near future we’re going to see more government/NGO money going to support contract drug discovery in big pharma – that is part-way to the same goal of removing the need for excluding people from the process.

    The open competition structure was applied in the Matlab programming competition – an open process, with a prize, where everyone can see the previously-submitted solutions. Yes, this means you are able to tweak someone else’s solution a little and submit it as your own, but this is surely the way to get to a good solution most quickly.

    The open source drug discovery project I’m part of has a completely open structure (without the prize) as spelled out in the six laws. It’s crucial the structure is a Baran map (a redundant network), not a Legrand Star where everything goes through a central point (Linus doesn’t scale). The needs of the project need to be clear, and the structure must be such that anyone can take part. The network also needs to have redundancies and be robust. Changes to the structure have to be easily accommodated. So can such an open arena be combined with a prize? There are lots of things to think about here, and one of the reasons we haven’t deployed a prize yet is because we want to get it right. We don’t want to set something up that is too small, or with the wrong structure. How do we ensure that participants contribute everything into the public domain? Will the money pervert the incentives, possibly irreversibly in the sense that when the competition is over there will be a serious drop off in participation (as in Deci’s classic study on intrinsic/extrinsic motivation (PDF)).

    I’ve been talking a lot about this with a talented guy I know, Jaykumar Menon. Jay secured resources from the Rockefeller Foundation to host a meeting to address this issue for a few days in 2014 at their Bellagio Centre, and now we’re setting it up and organising who’s going. I’m starting to talk about it now to garner insights people might have in advance. It’s very exciting. I’m optimistic that in those few days we can thrash out a good way to do this – make a competition long-term useful and actually effective.

     
  • mattoddchem 3:58 pm on September 25, 2012 Permalink | Reply
    Tags: chemical industry, CROs, , osddmalaria, philanthropy, pro bono   

    Companies and Open Science 

    There is an argument that says we should not be making simple compounds in academic research labs, but rather using specialist services to make molecules with which we then do interesting science. There is a lot of truth to that, particularly with medchem projects involving structures that are simple, or for which there is synthetic precedent. We’re making compounds in my lab as part of the open source drug discovery for malaria project because we’re trying to drive a unique way of doing things in the open and show that that works, but if everyone started doing open source drug discovery, and it became the standard way of doing things, I wonder if the process would be more efficient if we used a network of CROs, or even a set of super-labs specializing in synthesis (a proposal I’m thinking about, but I can’t decide whether it should be government- or industry funded). I think Elizabeth Iorns of Science Exchange has mentioned this idea too.

    The potential for CROs to make an impact on open projects is great. This is because an open source project consists of a nimble network. In regular research projects, funded by government grants, one will typically define the project structure at the start, cost up the resources, and then carry out that research in a manner that is closely related to the proposal. Naturally there will be variations in science and approach, but there are usually not huge variations in the structure of the team. Indeed, if there is no clear plan of how to carry out the research at the outset, that can be viewed dimly by referees. If the structure of the project changes dramatically during the funding period that can often require explicit reasons in end-of-project reports. There is thus some incentive in keeping the project as-designed. There may also be professional or emotional ties that mean a team is kept together even if it turns out it’s not the best team for the job.

    In contrast open source projects demand a nimbleness – that people get involved if needed, and that the required people may not be those defined in advance. I have found this challenging to explain in grant proposals, where I have tended to define project participants at the outset, and mentioned that the team will adapt and change in a process that is not fully controlled. I try not to highlight it too much, even though I know the ever-shifting project structure is one of the great novelties and strengths.

    So open projects are strong because of a loose set of transient connections. Interestingly this kind of network was recently shown to result in more cooperative behavior than networks with strong, more permanent connections between members. It’s a model, but an interesting one that to some extent mirrors what we’ve seen in our open science projects.

    Nimble projects can use small inputs from a number of people if needed, and those people, once they have contributed, have no obligation to continue to contribute. An open structure relies on enthusiasm and available resources and is very good at accepting small components from many people. This kind of project takes much more coordination, and is more complex, but should ultimately be more efficient provided there is strong, open management.

    So if we want to evaluate a series of compounds in a medchem program, for example, where the compounds are not necessarily methyl-futile analogs, but consist of different structures that may require different kinds of chemistry, it makes more sense to break up the work involved, and have several labs make a small number of compounds in parallel. It makes particular sense if there is a lab somewhere with expertise in the synthesis of a particular structure class, for example, who might be able to make that kind of structure quickly.

    CROs are set up perfectly for this, since they could make a single compound for a project during a short (1-2 week) downtime for a lab member, and then once that compound has been made they are not required to be involved any further. Rather like a bit torrent client that uses spare capacity in short bursts.

    The CRO marketplace is crowded and, I’m guessing, working with tight profit margins. Naturally companies are under pressure to attend to their core business. So why would a CRO want to contribute to an open source project? Several reasons:

    1) PR argument 1: If the project is philanthropic, the company gains a positive public image for contributing to the solution of that problem.

    2) PR argument 2: By performing the work in the open, where all data are shared in real time, a company can demonstrate its technical prowess, i.e. onlookers can see how fast a company can work, and the quality of the work in detail and in a real case scenario. Big pharma could observe the quality before contracting the company for new work.

    3) Employee satisfaction I: I believe (without data) that people are people and that employees working on a philanthropic project gain professional satisfaction from doing so.

    4) Employee satisfaction II: Scientists like to solve problems, and a challenge in parallel to one’s paid work, particularly if part of a team effort, is satisfying. Those taking part will likely secure publications.

    5) Exploitation of Unavoidable Downtime: Even an efficiently-run CRO will have periods of a week or so where an employee is not fully occupied. That spare time can be put to good use with the kinds of small contributions needed by open projects.

    6) Philosophical Agility: If a marketplace is tough, an edge is given to those companies who can distinguish themselves. Taking part in an open research project, which is an unusual thing to do, demonstrates a company is happy to think laterally and engage with ideas outside the comfort zone of their competitors.

    These arguments mirror those that I presume operate in what is an excellent model for what I’m proposing – the pro bono work performed by law firms. This is a major component of the legal profession. Now in many cases the big pro bono cases are those taken on by the big firms, and the analogous situation is the fantastic work that many of the big pharma companies are doing in philanthropic work for neglected tropical diseases – impressive and little-known by the public. One might argue that the CRO sector, which is more under pressure, cannot afford to contribute this way. I disagree, and return to the idea that an open project can be advanced by small contributions, appropriately coordinated. Rather than a CRO being locked into a collaborative arrangement for a long time, a CRO could be engaged in an open project (to make a molecule or acquire some data) for days or weeks before moving on to something more aligned with core business.

    What’s needed? Open data and an open research method will allow people to find and see what a project needs in a very responsive manner. But it’s imperfect since we may not search for the right thing, or the project participants may not record/coordinate their data in a way that is easily found. Perhaps instead we need a Clearing House for Contributions to Research. A place where people can say what work they need doing, and the clearing house tries to find companies who can do that work. Such a thing exists in law – PILCH – that matches those seeking pro bono work with those companies best able to provide that work. This mirrors the idea of the Molecular Craigslist I floated – where people could upload structures of molecules they need, and people can bid to provide those, i.e. needs-driven, not supplier-driven.

    Science Exchange and Assay Depot are like this, but again the process is not open (as far as I know). Thus I can request a service and receive quotes/offers (though to be clear I’ve never tried that) but I suspect the bidding process is not an open market auction-style. I’d like to see an open variant where there is a genuine process of bidding, in case someone wants to provide a molecule or service for free, for example, or in case the open procurement process itself could stimulate interest in contributing to the project. Perhaps Science Exchange and others could have an option to make the matchmaking process open. i.e. I need X, who would like to provide it?

    To date I have pitched the idea of contributing to the open malaria project to three CROs. One didn’t reply. One said they weren’t interested (but from the response I suspect my request was not well understood) and one said the following, to paraphrase: “Thank you for your mail. This request is very innovative. We are not interested in taking part because no other CRO is currently taking part”. I found this last reply quite interesting because the logic to me was the reverse of what I had expected. To me, it would have been a plus that nobody else was doing open source work, since were I to take part that would distinguish my company from all the others.

    So we’re going to be sending out more requests to CROs to make molecules as part of the osdd malaria project – at the time of writing there are several that are still needed. If my arguments above are right, there should be interest from the CRO sector. The question is how best to engage with that sector.

     
    • bill 5:31 pm on September 25, 2012 Permalink | Reply

      I work at a biotech firm not a CRO, but I occasionally contract out work — mosty manufacturing and clinical stuff. From the little I’ve seen, your arguments should carry weight (well, 3 and 4 are less meaningful to the business types). My experience has been that it can take 10-20 attempts to find a good match, so you’re right not to be discouraged after only three. You write well so I probably can’t improve it, but I’d be happy to take a look at your intro email if you like.

      • mattoddchem 10:53 pm on September 29, 2012 Permalink | Reply

        Thanks Bill. I’ve posted the draft email here: http://bit.ly/SVuRqu. If you’ve time to take a look, that’d be great.

    • Elizabeth Iorns 10:26 pm on September 25, 2012 Permalink | Reply

      Very interesting article! We could certainly have an ‘open project’ option – I’ll ask our developers how difficult it would be to implement and get back to you – thanks for the suggestion!

    • Cameron Neylon 6:53 pm on September 26, 2012 Permalink | Reply

      I can see at least one other reason why a CRO would want to contribute (even on a pro or low-bono level) and that is to grow what is potentially a massive market for them at relatively low risk. By creating a larger pool of projects operating in this nimble fashion there is significant potential to grow up a paying market in which researchers purchase their services because its the most cost effective way to get things done. But that market has to be created.

    • Kevin Lustig 2:16 pm on October 3, 2012 Permalink | Reply

      When we started Assay Depot 5 years ago, we thought about setting up a commercial bidding process in much the way you describe. We envisioned that scientists would come to the site, list what they needed and get bids from any interested vendors. Scientists and vendors, however, were less than enthusiastic about the idea. We found that many scientists, particularly from biotech and pharma, did not want to post their requests publicly, where they would be visible to their competitors. Vendors also did not like an open bidding process, in which their prices would be visible to possible competitors.

      Our solution was to create a taxonomy of 500 research areas, to identify vendors in all 500 research areas and to make it easy and free for a researcher to reach out privately to two, twenty or two hundred pre-selected vendors at the same time (and ask a question or request a quote). With some simple online tools we’ve built, it’s almost as easy to communicate privately with fifty vendors as with a single vendor. This approach keeps the entire set of conversations private, pleasing both scientists and vendors.

      I think your idea of an open matchmaking process for free services and capabilities is a good one. There must be hundreds of academic and industry laboratories that are looking for a collaborator in a certain area or that have excess capacity on an specialized instrument and are willing to use it for a good cause, without compensation or in exchange for in kind services. Looking out a few years, I can even imagine a thriving “research bartering” system that facilitates collaboration and enables global research partnerships for both small and large laboratories in academia and industry.

      • drgunn 10:38 pm on October 3, 2012 Permalink | Reply

        ” There must be hundreds of academic and industry laboratories that are looking for a collaborator in a certain area or that have excess capacity on an specialized instrument…”

        Isn’t that pretty much what Science Exchange does? They’re focusing on core facilities at universities, but it seems to me like the line between a “official” core facility and a lab that has a specialized instrument and wants to fill excess capacity is a pretty thin line. The whole point of the Reproducibility Initiative they’re leading, which Mendeley is also a part of, is to get some of this excess capacity put to good use. It’s not explicitly philanthropic, but if we can raise some funds, it will be, and anyways creating a collection of replicated high-impact work will help organizations such as patient advocacy groups and disease foundations.

        Speaking about open discovery more generally, there are few labs which really are working openly, as you all know, but once we shift the focus of academic achievement away from just getting citations towards a more reuse centered approach, there will be no reason why people don’t work openly. In fact, it will become essential for success.

        • Kevin Lustig 5:02 pm on October 4, 2012 Permalink | Reply

          I believe that we are headed toward a new era of science where we are all “service providers” to one another, an era in which we openly share our unique talents and work closely together in ways almost unimaginable just 10 years ago. That being said, I think it will take some years to get there.

          Until the enormous explosion in pharmaceutical research outsourcing over the last ten years, there was a clear division between academic core labs and CROs, which offer services, and research laboratories, which make research breakthroughs. One was clearly subservient to the other. Now that it is possible to obtain any research service imaginable from any university or commercial vendor through applications like Assay Depot (and at least 12 other research service matchmaking sites), the distinction is not so clear. Anyone can now access world-class experts in any research area, and anyone can obtain any research service, provided they have the resources to fund the work. In certain important ways, life science research has become decentralized and democratized.

          In this new era of science, research laboratories are still critical but they are no longer the center of the research universe. They are important because they provide one or more key services – the ability to ask the right questions, the ability to understand the relevance of data or the ability to create unique research services not yet commercialized – but they are now only one link in a chain of service providers required to make a breakthrough research discovery. It is this shift in perspective that I believe will be difficult for some to make and why it won’t be easy for the next few years to get the heads of research laboratories to post their “services” online in the same way that core facilities and CROs are generally eager to do. It will happen, but old habits die hard.

          • mattoddchem 8:31 pm on October 8, 2012 Permalink | Reply

            Agreed – I think it’s very interesting the way things are changing. Thus in many academic drug discovery projects, the synthetic chemistry is being done by PhD students because that’s the way it’s always been done. An argument is made that it’s good “training” but I worry about that. After one has made one small molecule by doing an amide coupling, there is questionable added value in making 10 more. The point ought to be that we are training our students to think about new ways of doing things, and that might mean involving specialist research services along the chain of experiments.

    • Bill Hooker 11:04 am on October 6, 2012 Permalink | Reply

      Finally got around to working on the letter:

      https://docs.google.com/document/d/1yUm1UdKuRczoj8f-DjEQbQnyuNPIbxK7GQUuD2FpNnk/edit

      I made a new copy because I didn’t add anything substantive but I shortened and rearranged, which got ugly fast when I was trying to just leave comments. My experience has been that shorter and punchier is better, when reaching out to industry/business partners.

      Hope that helps some.

      • mattoddchem 8:32 pm on October 8, 2012 Permalink | Reply

        Sincere thanks Bill – excellent. Will finalise and start sending out as soon as I overcome a minor inbox bubble.

    • Kevin Lustig 8:56 am on October 7, 2012 Permalink | Reply

      We’ve recently been trying a variant of your idea together with Jimmy Lin and his colleagues at the Rare Genomics Institute. We set up a Rare Disease Science Challenge for kids with rare diseases. We then reached out to the over 1100 vendors in Assay Depot’s network and asked for in kind donations of research services for the Challenge, including assays, models, consulting time, informatics tools etc. To date we have received commitment for more than $375,000 in services (and 10K cash) from a total of about 25 research vendors. After the launch of the Challenge on October 15th, the Rare Genomic Institute will team up families with research experts, who will use the donated services to craft an individualized drug discovery plan for each sick child. A team of well-known experts including Atul Butte from Stanford and Bernard Munos from Innothink will help judge the proposals. Facebook voting will determine the final winner (or two). Here is a link to a recent blog post if you are interested in getting more information: http://blog.assaydepot.com/rare-disease-science-challenge-call-to-action

      We spent about 2 months soliciting donations and, although 385K is not insubstantial, I was a bit disappointed in the vendor response (25/1100 = 2.3% response rate). The success we did have was clearly due to the fact that we had a very compelling story. Most rare disease patients are kids that die before age 10, and despite the name “Rare Diseases” affect 1 in 10 Americans so many people are directly or indirectly affected by a rare disease. I also believe that the vendors got involved because they felt that it would be good marketing exposure they could receive without a cash payment.

      If you are interested, we’d be happy to help get the word out about your open science work directly to our network through our monthly vendor newsletter.

      • mattoddchem 8:28 pm on October 8, 2012 Permalink | Reply

        That’s very interesting, Kevin. Yes, this is similar to the idea I outlined. Your success rate gives an interesting guide to how many CROs we might have to contact here. In answer to your kind offer, then yes we’d clearly love to be brought to the attention of your network. We’ve actually submitted a request for synthesis of a few compounds in the usual way. The relevant structures are here:

        http://www.thesynapticleap.org/node/416

        …but if you could flag up the need for a few mgs of the specified structures, with perhaps a link to this blog post, that would be enormously helpful, thank you.

    • mattoddchem 10:01 pm on October 8, 2012 Permalink | Reply

      Some more background on PILCH, and how it coordinates the supply and demand of pro bono activities.

      http://www.liv.asn.au/News-and-Publications/Law-Institute-Journal/Archived-Issues/LIJ-October-2012/In-the-public-interest

  • mattoddchem 9:14 pm on April 24, 2012 Permalink | Reply  

    Sage Commons Congress 2012 

    I was at the Sage Commons Congress the last few days. Meetings should be full of challenging new ideas and full of spontaneous discussion. I’ve been to a lot of scientific meetings where both those things are absent (shockingly, actually) or where the meeting brings little beyond what could be learned from the literature. This congress was very interesting, driven by the passion of those people taking part to do science in new ways.

    Lobby of the Hyatt Regency from the 15th floor

    Sage has a mission to understand disease. I had thought that the plan was to assemble and share very large amounts of scientific data. That’s essentially true, but I realise I missed two things. (Many of the talks can be found here – I won’t link to individual talks because the non-skippable sponsor message is too annoying each time.)

    1) The word “disease” is becoming a little redundant. The philosophy of the group at this congress, but I’m not sure how far beyond, is that the idea of a single “disease” as a static thing that affects everyone equally, is of limited usefulness. People respond to therapy differently. If you accept this then what’s left is not a disease but a “disease-patient-medicine interaction” – a dataset that includes the patient’s biota (DNA, age, habits etc) and also more nebulous factors (how are they feeling when they’re being given therapy).

    Given that patients are volunteering to contribute their data in ever larger numbers, it is important to use such data to understand whether a therapy works and whether a therapy is likely to work for a new patient.

    If more patients are sharing their data, then it’s important we are on a firm legal grounding. Synapse, the Sage system demoed at the congress for collaborative data sharing, requires patients thinking of becoming involved to give clear consent for the use of their data, and John Wilbanks described a system he’d been working on called “Portable Legal Consent”.

    A related idea is that patients should be involved in research – that researchers should be listening to what patients have to say about what is needed for their disease. From my perspective, as someone who works with early-stage drug discovery, this seemed rather an alien idea. It’s also interesting that the diseases discussed in this way were almost all developed-nation diseases. In practical terms, for malaria and NTDs, patient consultation comes second to a broad morbidity-reducing treatment.

    Embarcadero

    2) A persistent theme at the congress was that we know little about disease, and what we do know is rather too academic. Rick Klausner gave a real demolition of academic understanding of medicine, more or less saying we ought to start from scratch, it seemed. And there were many voices raised in concern at reproducibility. I hadn’t realised this was so serious, but a Nature editorial raised the issue a few weeks ago and the conclusions are not good no matter how you look at them. One really dreadful example came from Jamie Heywood, below.

    Synapse is a platform allowing sharing of data, and collaborative tweaking/reuse. Platforms/Apps are important, but there is I think sometimes too much emphasis placed on the importance of collaborative workspaces (several new platforms were announced during the congress). My view is that we allow people to develop whatever tools they need, provided the code is open source, and provided there is interoperability. Standards in data sharing are what’s important. Let the community define the software it needs for a given task, and insist on interoperability (Blue Obelisk is trying to do this for cheminformatics). I think that Synapse is due to be open source, so that people can install their own local versions, which would be a smart way of increasing its prevalence.

    Bay Bridge

    Three talks were highlights for me (the only times I stopped Tweeting because I was so interested):

    1) Adrien Treuille‘s description of Foldit and EteRNA, and the emphasis he placed on the impact participation had on the participants. The other wonderful element of those projects is the reciprocity – that the techniques developed by the humans for solving these problems were incorporated into next-gen algorithms for the computers, but that then the humans, seeing what the computers weren’t good at, started to set problems for the computers which were difficult because they knew (and felt sorry for) the machines’ weaknesses… He paid nice testament to the power of human learning.

    2) Larry Lessig’s wonderful rant. It was a call to arms against the corrupting influence of publishers – corrupting not in an evil way, he was clear to say, but because profit-making is in a publisher’s nature. It can no more be blamed for that as a tiger can be blamed for being fierce. But the message, delivered in the final two minutes in response to a question, was that even if there appears to be no solution to a problem, we still work to do something out of love. I suspect this is the motivation behind many in the open access movement, that even if solutions to scalable, sustainable, economically viable open access literature seem too difficult, we still pursue them for love of the corpus of human knowledge.

    3) Jamie Heywood. He spoke movingly about the reasons he set up the ALSTDI, and I was fascinated at the supreme success of such a non-profit drug discovery organisation vs. its commercial competitors, and how much effort it must have taken to set that up and keep it running. The awful part of this talk, however, was the reproducibility study he carried out, burning millions of dollars to show that the then-preferred/recommended lab-based therapies had no clinical efficacy. Tragic, awful and jaw-dropping. One can’t help but extrapolate from that study and one is then awed by the dreadfulness of the message.

    Cinderella were there (though I could not sense how open the work was that they were doing) as was something called Discovery Network, but I could not understand what that organisation was. Nobody else appeared to be doing open drug discovery of the kind that we are doing, but the focus of the meeting was much more on the translational/late stage side.

    A competition was announced called DREAM which will be on finding new algorithms for the analysis of breast cancer data, but it’s so new that there are no links yet. It reminded me of the MATLAB competitions, and I hope that they run with a similar idea, that the intermediate solutions submitted are rewarded as well as open, so that others may build on earlier solutions.

    It was a pleasure to meet others, such as Kelly Edwards, Kaitlin Thaney (finally), Elizabeth Iorns, Bas Bloem, Lance Stewart from the Allen Institute for brain science, Sarah Greene from Cancer Commons. Significant kudos to Stephen Friend for organizing (and to Jon Izant who was dealing with things behind the scenes and who was kind enough to invite me to come along to begin with).

    The “Hows” rather than the “Whats” of operating distributed communities of science were requested, and Stephen requested we call out people on things we thought were right or wrong. To my mind the idea of openness wasn’t sometimes emphasized as much as it could have been – the Federation of Phase I of Sage, for example, is essentially a large, closed collaboration between existing groups which does not make use of the power of interested strangers. When openness was mentioned it was often within the context only of data, not of workflow, or process. Open data for me is step 1, but then working with people openly is the extra value of open science – describing what one is doing, what one needs, where a project is going, what our failings are as human scientists. This interests people, and informs people of what is needed next. It acts as an education of what science is. A description of the process behind the data acts as the ultimate metadata, in other words.

    I am also reminded of how extraordinarily behind the times chemistry is with regards open data compared to the biologists, who just seem to get it. That’s for another post. But if understanding of a disease is being raised as a real problem in medicine, we ought to start talking about the lack of predictability in chemical synthesis. Or to what extent proprietary chemical data will be first against the wall when the revolution comes.

    Cameron Neylon’s post on the conference is already up. Thanks to him and Mr Gunn for a hangover that almost got in the way on Day 2. Thanks to Adrien Treuille for making me forget it.

     
  • mattoddchem 6:01 am on April 20, 2012 Permalink | Reply  

    Molecular Craigslist 

    I think we need an eBay for molecules. Or maybe a Craigslist.

    We’ve identified some potent new antimalarials in the open source drug discovery for malaria project that are already being investigated in vivo. The series seems interesting, and we may need to explore it fully if the biological results are good. We may need to make a bunch of analogs, but we don’t want to spend time making molecules that are commercially available. Iain Wallace has been doing some lovely analysis of which compounds similar to the new hits are commercially available.

    I had a very interesting meeting at UCSF Mission Bay with John Irwin this morning which made me realize we ought to be using Zinc more. A quick search around our most potent hit threw up these commercial compounds, for example. We ought to check them out.

    Given we can identify relevant, commercial compounds we now need to contact suppliers to see if they might donate.

    But we can do more than that. What about compounds that might just be sitting in fridges in academic labs? A quick SciFinder search led us to this paper, and we’ve contacted the relevant group at Scripps to see if they might share some compounds.

    But we can do more than that too. Imagine there is a group somewhere with expertise in making these kinds of compounds, and who might want to make some analogs as part of a student project, in return for collaboration and co-authorship? What about a Uni lab which might be interested in making these compounds as part of an undergrad lab course?

    Wouldn’t it be good if we could post the structure of a molecule somewhere and have people bid on providing it? i.e. anyone can bid – commercial suppliers, donators, students?

    Is there anything like this? Well, databases like Zinc and Pubchem can help in identifying commercial suppliers and papers/patents where groups have made related compounds, but there’s no tendering process where people can post molecules they want. Science Exchange has, I think, commercial suppliers, but not a facility to allow people to donate (I may be wrong), or people to volunteer to make compounds (rather than be listed as generic suppliers. Presumably the same goes for eMolecules, and Molport?

    Is there a niche here for a light client that permits the process I’m talking about? Paste your Smiles, post the molecule, specifying a purpose (optional), timeframe, amount, type of analytical data needed, and let the bidding commence?

    Benefits to this Molecular Craigslist are:

    For Businesses: Business
    For Donators: Good PR and possibly a collaboration
    For Students/PIs/Synthetic Chemists: Possible collaboration and authorship.

    Easy to make such a site?

     
    • Chemjobber 8:26 am on April 20, 2012 Permalink | Reply

      I am not a chem-informatician, but I believe that the Available Chemicals Database is supposed to service a portion of this function. Problem is, of course, that just like Craiglist, the ACD has been spammed to death of recent years.

      A company saying that they have a compound on the ACD is not the same as them actually having it.

      • mattoddchem 8:37 am on April 20, 2012 Permalink | Reply

        Right. My conception is needs-driven. If you *want* something you list it, rather than if you’re selling. And with Craigslist the site is not involved in the transaction, which is also good.

        I should mention that another relevant site is Innocentive. That, to date, has been for larger competition-type requests, rather than micro-requests. There are rewards/incentives etc. And of course the site is involved in the transaction, with paperwork that allows secrecy in the dealings between the party that offers and those who want to solve. Craigslist keeps that to a miniumum by, at most, anonymizing emails. But it lets buyer and seller negotiate directly, with small transactions.

    • Chemjobber 9:11 am on April 20, 2012 Permalink | Reply

      Yeah, I’d be for it.

    • Mike 8:55 pm on April 20, 2012 Permalink | Reply

      This may (but in all likelihood not) be potentially suited to sites similar to Freelancer.com that really started out as a way to outsource (in a very cheap manner) relatively simple web design/logo design tasks. The categories on the site don’t really reflect a remotely chemical/biological basis (more categories at http://www.freelancer.com/sellers/) , but in part I’m sure that’s due to the fact that this probably hasn’t been trialled much.

      It’s a start but I think the reward/incentive system would need tweaking for an academic context.

    • bill 2:05 am on April 21, 2012 Permalink | Reply

      Bioroot was an early attempt at something very like this. It died of neglect (not the developers’ — the potential users’).

    • mattoddchem 12:25 am on May 16, 2012 Permalink | Reply

      Chris Southan made a nice survey asking whether companies would be willing to get involved in supplying compounds to philanthropic projects:
      http://www.surveymonkey.com/s/SXXZDX9

    • Dr. Alex M. Clark 9:29 am on May 24, 2012 Permalink | Reply

      Something like this might be quite a good fit for the Open Drug Discovery Teams (ODDT) app (http://molmatinf.com/products.html#oddt). The mechanism by which the server harvests chemical data originating from tweets with particular hash tags seems like it would provide a good fraction of the functionality up front – or at least enough to establish social proof, with more features added later if it catches on.

      We could create a new topic called “Mat’s List” (#matslist)… or something a bit more general if you don’t feel like taking all the credit for it :-)

    • Paul Ylioja 11:40 am on May 28, 2012 Permalink | Reply

      Just read an old Nature article [http://dx.doi.org/10.1038/news040816-14] that mentions Eli Lilly’s internal drug candidate “Stock Exchange” for predicting which compounds are likely to make it to market. It would be nice to know more about their system. Is it still going?

    • Wolf-D. Ihlenfeldt 3:15 am on July 7, 2012 Permalink | Reply

      Why re-invent the wheel?

      Innocentive (www.innocentive.com) provides the functionality requested, has been operating for many years, and built a reputation…

    • Alex Hoekstra 8:43 am on July 8, 2012 Permalink | Reply

      What about Assay Depot? It’s fundamentally like Amazon.com for science. You can contract research, chemical synthesis, reagents, supplies; compare prices; read and write ratings and reviews; browse catalogs and services; contact organizations directly…it’s pretty neat.

    • Sean Seaver 3:35 pm on January 19, 2013 Permalink | Reply

      We get a lot of requests for products and the vast majority are fulfilled by locating items from existing sources. As you mentioned the Zinc database contains 28 million compounds and sorting through this information can be difficult and very time consuming for researchers. I wonder what would be the demand for a platform for requests, it’s certainly an interesting idea!

    • mattoddchem 9:40 pm on May 12, 2013 Permalink | Reply

      A related idea from John Irwin at UCSF – but again, people offer molecules, as opposed to someone posting what they need and asking for suggestions/collaborators.
      http://zinc.docking.org/browse/catalogs/collabocules

  • mattoddchem 10:54 am on April 19, 2012 Permalink | Reply  

    Reinventing Discovery on the way to the Sage Congress 

    I’m in San Francisco for the Sage Commons Congress, and am excited to be able to contribute. I took a United flight, and there were no TVs. I was also surrounded by loud people, so couldn’t sleep. To salvage the 13 hours I read Michael Nielsen’s Reinventing Discovery, finally. It’s testament to the quality of the writing that I glided through it in one sitting (I did have a window seat). The book makes some wonderful points, and I’d recommend it to anyone. I wonder if Michael’s call to arms about the absurdity of the current model of scientific publishing was more scathing in earlier drafts, and that the original version might be accessible by giving Michael a beer. A few random things I enjoyed:

    1) The optimism of our knowing about collective knowledge from Ostrom and others, and how that might allow us to progress to a change in the way science is done (from the top down, guided by informed decision making). I had previously written about the relevance of Ostrom to open science communities, in a brief post.

    2) The wonderful public hissy fits one can read in open source software project sites, and how that adds humanity and interest to the process of work. It sounds like a similar thing happened in the Kasparov vs. the World chess game. There’s precious little of this in science.

    3) The irony of our current publishing system, that actually inhibits distribution of information, whereas it was set up to do the opposite.

    4) The wonderful section on what computers are good at vs. what humans are good at, and how this leads to a reinterpretation of what “understanding” is or how a “model” is perhaps more than that. I enjoyed the section on the Google Translate project (wasn’t that the DARPA project)? Successful through a statistical modelling of language uninformed by grammar.

    5) I liked the comment that open drug discovery might be a step too far, given the IP ramifications. Well, we’re trying that, so let’s see!

    6) Michael’s comments on the possible limitations of citizen science projects like Galaxyzoo and Foldit were also very interesting. These are spectacular projects, and the comments were addressing whether there were many other projects where the public could reasonably be expected to input productively. My view is: Yes, and I hope so… I think this is a transformative challenge, in that it would be so sensational if the public could contribute to hardcore science through good project design. I, for example, want to see the public able to contribute to projects in the design of new catalysts. The challenge is to design a system where that becomes possible. That’s extraordinarily tough, and hence worth doing.

    I hope Michael will soon be able to write a sequel to the book, Discovery Reinvented.

     
  • mattoddchem 9:26 am on January 30, 2012 Permalink | Reply  

    Wikipedia vs. Academic Papers – a Middle Ground 

    We’re trialling an experiment until the end of February. Can we assemble a review of an area of science on a wiki, allowing anyone to contribute, and then publish that in a peer-reviewed academic journal? (early description of this on G+)

    Wikipedia has a great deal of useful information, but its coverage of some academic areas can be patchy – it naturally depends who has contributed. With many articles the reader will be unable to judge whether the article is complete and accurate according to the current knowledge of the field. By contrast, many academic articles in journals are not open access, reducing the readership. Sometimes articles are written with a significant bias towards the authors’ work, and indeed sometimes that is the explicit purpose of the article. It’s very rare for leaders in a field to get together to co-author a review.

    Wikipedia also has a suspect reputation in academia – we complain about its shortcomings, do little about it, and then all go and use it when nobody is looking.

    What if we could assemble a paper openly, using a consortium of interested people, and then at a point where everyone is happy that the article is complete, we submit it for peer-review and publication in an open-access journal? That would have the disadvantage of killing off future edits (because the paper was reviewed as a static object) but the great advantage of producing a citeable article that would be curated by the journal. One could donate the final version to a relevant Wikipedia page, but the article is guaranteed as peer-reviewed, and has a DOI, etc.

    We attempted this with our resolution paper last year. The research article we wrote was based on public-domain knowledge arising from our open online electronic lab notebooks. It was written on a wiki where anyone could contribute. It was submitted to a journal, reviewed anonymously and then published. In that case nobody outside the core team (the listed authors) contributed to the writing. They could have, but in the end did not.

    The chemistry in question was, to a first approximation, solved. What we’d like to do is find a second solution to the problem that uses more sophisticated science (which is more expensive, perhaps prohibitively, but that’s OK at the moment). The area of science that is relevant is a certain chemical reaction – the catalytic, asymmetric Pictet-Spengler reaction. In the course of doing this research we’ve been looking back over what’s known of this reaction and when one does this one can’t help thinking about writing a review. We thought it would be interesting to generate such a review in the open, allowing anyone else with an interest to participate.

    The current draft is here. The talk page contains what needs to be done and allows a trail of author interactions. Two of my students and I have to date done most of the work. Three other people have expressed firm intentions to edit the document and add sections. We have applied a time limit to the writing process of the end of February because that’s when semester starts in Sydney and it would be nice to be finished with it by then. A Dropbox folder contains all the relevant things – pdfs of relevant papers and the raw files used to generate the diagrams. People working on the paper have access to that.

    This experiment in writing chimes with what a few others have been saying about the review process (my summary with links is here). Tim Gowers, for example, has been talking of a possible website where papers could be deposited as drafts (arXiv style) and then people be allowed to review them for improvement before submission. There is an interesting discussion to be had there about a “currency” of peer-review – that if someone undertook some editing of an article, could their contribution be reciprocated, maybe quantitatively? This goes to forming an incentive to participate in peer review, and also goes to how we could build reputation in academic circles – an attractive idea for younger scientists who would like to engage in writing papers and building careers, but for whom there is no clear way to do so because they lack the usual academic monikers. Currently professors do peer review (or are meant to) yet have no great incentive to do so beyond the better parts of their nature, and graduate students may be involved but receive no recognition outside their groups. Can lessons learned in open source software construction be applied to writing papers? How would the infinite gradations of expertise work? Would there need to be restrictions on permissions to authorship based on one’s current standing in such a system? These are really interesting questions that go to the future of how we write papers, so this experiment is an attempt to look at those things.

    Fundamentally what we’re proposing is simple – people get together to write. Everything can be checked and edited. We have instituted a “quality control” section in the talk page to ensure that everything written is checked by at least one person, who identifies themselves. I have assigned myself as corresponding author to ensure the buck stops with someone. I am keen, for example, for the review to be well-written besides just being correct. I have read a lot of perfectly correct reviews which often require a lot of coffee.

    The challenge of this model is this: How much work constitutes authorship? I don’t know. That’s the purpose of the experiment. At this stage, with a small number of participants, I can do this manually. If I think someone has contributed significantly, I will allow that person to be named. If the contributions are minor, that person will be “acknowledged”. It is possible for a student to be named, but not their professor (very much not what happens in my discipline) but I am making it clear to anyone volunteering that I have to check that with whomever is paying their salary, because I’m polite like that. It is certainly possible that if someone does a very large amount of work on the review, taking it in new directions or rewriting large chunks for the better, that that person should become (a) corresponding author, because being corresponding author means taking ownership of the end result.

    It’s certainly been an interesting process thus far (20 days). Writing in this way feels “live” – edits can come at any time, from anywhere. There is a history of the page so things can be tracked and undone. The writing has gone quickly, apart from in the last five days where my students and I each independently became involved in other things that took us away from writing. But the fundamental aim is: to produce a complete, high-quality review of an area. I am very interested to see if that is what happens.

    Where to submit? I’m considering the small number of options in chemistry. PLoS ONE does not publish reviews.

    I’d also be grateful for any related examples of distributed paper writing where the draft assembled in the open then went to peer review. I am assuming that the papers arising from the Polymath project (rather than just the project itself) were constructed by multiple people, but if anyone knows of other cases, please say.

     
  • mattoddchem 11:02 pm on January 26, 2012 Permalink | Reply  

    Goodbye Elsevier, Goodbye Tet Lett etc 

    I’ve decided to stop refereeing for, and publishing in, Elsevier journals. I was just asked to review for Tet Lett again, and sent notice that I’m out:

    “Apologies, but I have decided to stop refereeing for (and publishing in) Elsevier journals because of 1) the lack of a positive policy towards open access (to all content, not just individual articles) and 2) Elsevier’s aggressive commercialism, in particular its sponsorship of the Research Works Act in the United States which would unquestionably harm science. Please remove me from your list of referees.

    If Elsevier were, in the future, to decide to support full open access to the academic literature I’d be delighted to resume refereeing duties.”

    Over the last few years my interest in open science has grown, and inevitably I’ve had to confront the power of open access literature, which is a necessary condition for open science if we are to avoid the absurdity of research conducted in the open disappearing behind a subscription once it’s done. My doubts about contributing to a system of closed access journals, which totally dominate organic chemistry, were becoming overwhelming when Tim Gowers’ post came along about the need to declare publicly that we would no longer support the system.

    I’m starting with Elsevier. The tipping point was the ridiculousness of the Research Works Act – a squalid little affair that was very little to do with the greater good or the benefit of science. I have been irritated by all the pompous talk of the “value” Elsevier adds to the process of peer review. Over the last ten years or so I have had experience of the peer review system operated by 3-4 organic chem Elsevier journals. I’d like someone to point out something about this “value” that is innovative or surprising and which might need some hefty R&D budget. Is it perhaps the case that simply publishing an article written and reviewed by scientists has become fairly straightforward in this modern age? I have been an editor at PLoS One for a while now – ironically a journal that some people still think has no peer review system. The peer review I have managed for papers there (managed by scientists, backed up by editorial staff) has been rock solid, lengthy and rigorous. I have zero data to back this up, but it feels as though more people reviewing for PLoS One care about what they’re doing than do those reviewing for some of the Elsevier org chem journals. PLoS One is also trying hard to innovate in the area of article-level metrics.

    As a chemist, parting company with Tet Lett in particular causes mixed emotions. The journal has a weak reputation amongst my co-workers and colleagues these days, but of course there are classic, beautiful papers in there, like Corey’s PCC paper, or seminal reports of Sonogashira couplings and Weinreb amides. My last paper there from 2009 has been cited 20 times already. My first paper was published there. I feel like holding a wake. But good science is not the product of a journal, it’s the product of hard work by people. The last thing we should be doing is paying anyone over the odds to access it back or giving anyone copyright over it. A sad day, but times change which is why times are interesting.

    If you want to join the boycott, you can declare yourself here. You’d be in very good company, in case you think this is just a list of naïfs.

    Eventually I will have to take the same stance on other publishers, with the American Chemical Society looming large. I need to consider the welfare of the students in my group, and their CV’s. It’s really very tough in chemistry – people expect papers in certain places. The ACS is technically a learned society, and has a healthy contribution to the blogosphere etc, but something about its control of the literature just doesn’t feel right. If the data in Scifinder were donated to the public domain chemistry would have its Human Genome Moment.

    My last two papers were in ACS journals because these were the most appropriate places for the students’ work, and because the prestige of the journals helps my students. They were both thoroughly reviewed and published quickly. But this just can’t go on, and I suppose I must soon stop interacting with the ACS too. And, I guess the RSC. One step at a time. With the bigger journals that deal with significant papers and publish items beyond research articles the sense of “value added” is perhaps clearer, too, and the discussion becomes economically more complex. Yes, I’m talking about you, Stuart – if Nature Chem went author-pays, it’d be ($ a lot) per article, I seem to remember.

    I’d be interested to hear from other chemists. It feels our discipline is the most traditional, and almost completely beholden to closed access publishers. It feels we care less about open access than scientists from other disciplines, and that we’re too comfortable with out lot. Comfort is the death knell of academia. We perceive the transformative benefits of open access to data too little, in particular the re-use and mining of large open data sets: the immense power of tinkering, re-mixing, playing. The lack of unrestricted play with the accumulated knowledge of chemical reaction outcomes is one of the key weaknesses of the way we are doing organic chemistry today. For that we need open data. That means open access to the literature.

     
    • antonywilliams 12:46 am on January 27, 2012 Permalink | Reply

      Mat…do you know the RSC’s position on Open Science? Your comments welcome: http://www.rsc.org/Publishing/Journals/OpenScience/FAQ.asp

      • Peter Murray-Rust 3:05 am on January 27, 2012 Permalink | Reply

        Tony, in answer to your question…

        As far as I can see authors can pay 1600 GBP for “RSC Open Science” http://www.rsc.org/images/GeneralLicence-OpenScience_tcm18-64482.pdf. This licence is nowhere near BOAI compliant and requires depositions in a specific repository for non-commercial purposes. It would, for example, prohibit Chemspider from re-using any part of it (before Chemspider became part of RSC). It contains phrases such as:

        > the Owner grants to the RSC the exclusive right and licence throughout the world to edit, adapt, translate, reproduce and publish the Paper

        >The Author(s) may make available the accepted version of the submitted Paper via the personal website(s) of the Author(s) or via the Intranet(s) of the organisation(s) where the Author(s) work(s)

        >Persons who receive or access the PDF mentioned above must be notified that this may not be further made available or distributed.

        >No deposited Paper, whether in an Institutional Repository, Funding Body Repository or personal website, may be forwarded to any website collection of research articles without prior agreement from the RSC.

        In other words the RSC has complete control over the re-use and distribution of the paper.

        It effectively denies *anyone except the RSC* the right to:

        re-use diagrams from the paper
        translate spectra into something useful
        translate parts of the paper into a foreign language
        text-mine the paper

        and even download it from the author’s repository and print it (that is unauthorised distribution)

        The licence is RSC-specific (not Creative Commons) so there is an additional overhead in reading it.

        This is not Open Access according to BOAI.

        Please correct me if the facts are wrong. I am not offering my opinions :-)

        .

    • Peter Murray-Rust 1:28 am on January 27, 2012 Permalink | Reply

      Matt,
      It’s not just pricing, grooty journals, arrogance, etc. It’s about our ability to do what we like without research. My group has built software which can extract a large percentage of reactions out of Tet. Lett and Tetrahedron. If I try to do this I’d be sued within minutes. We could build a system that would make CAS and Reaxsys look 10 years out of date (which they are). But the University of Cambridge would be cut off by Elsevier laywers. Elsevier have treated me with total arrogance, disdain and I … words fail me.

      There is a better future and it doesn’t include current publishers. We shall have to build it ourselves. It’s hard but possible.

    • Rich Apodaca 3:40 am on January 27, 2012 Permalink | Reply

      Mat – you’re an inspiration. Bravo!

      I’m curious – given the needs of your students to find work after graduation, which chemistry journals do you currently see as being: (a) most prestigious; and (b) most consistent with free scientific discourse?

      Also, don’t forget that prestige is fickle. Fannie Mae used to be one of the world’s most respected companies. Apple used to be a joke.

      ‘Author-choice’ journals don’t solve the problem, IMO. ACS and RSC – this means you.

      The future belongs to publishers who can innovate (yes, actually do something different and risk failing) to reduce costs, trim bloated, top-heavy organizations, effectively use information technology, and deliver value to the scientific community – while paying the bills.

      Despite plenty of hot air from publishers, I’ve not found a single one that in any way explained to the scientific community how they’ve done all of the above and still can’t:

      1) let authors keep copyright to their works; and
      2) let readers freely distribute and repurpose all journal articles

      Strangely, I see journals like Beilstein Journal of Organic Chemistry (http://www.beilstein-journals.org/bjoc/home/home.htm), which does both of the above and has been running for many years now.

      • mattoddchem 2:39 pm on January 28, 2012 Permalink | Reply

        Rich – In my field it’s all closed – JACS, JOC, Org Lett, Inorg Chem (for some of my stuff), as well as Angewandte, Chem Eur J, Chem Commun, the new Chemical Science as well as Nature Chem, of course (which is publishing a much smaller number of consistently cool papers). PNAS is very good, and as far as I know more committed to open access (after a delay?). The Beilstein journal is excellent – open access and no fee to submit – amazing. I published there (http://dx.doi.org/10.3762/bjoc.5.67). The current open access journals in my field are finding it difficult to get traction, but are trying hard – Chem Central J, for example. PLoS ONE will take chemistry, but the uptake by the community is slow. I’m on the board of the very new ChemistryOpen from Wiley, and we will see how that goes. For me the ability to pay something to make one article open just won’t do it – the rest of the journal is closed – I’m really interested in the bigger point about the ability to mine and re-use data freely as a spur to innovation. The journal becomes a formal repository – very useful and important as a portal to organised data.

    • Rebecca Guenard 6:16 am on January 27, 2012 Permalink | Reply

      Wow, good for you! That’s huge!

    • Heather Morrison 10:02 am on January 27, 2012 Permalink | Reply

      Bravo! As for past papers, a reminder that Elsevier is green for self-archiving – please liberate your works, get them to your local IR for open access!

    • Egon Willighagen 4:18 pm on January 27, 2012 Permalink | Reply

      Good luck! (Organic) Chemistry is not particularly know for caring about any of this (nor semantics, nor computing)… but I second Rich’ pointer to the Beilstein Journal of Organic Chemistry. And there is Chemistry Central too. What other gold OA options are there for chemists? There is Molecules as ChemComm replacement… others?

    • Tyrosine 4:21 pm on January 28, 2012 Permalink | Reply

      It’s a pretty easy decision for an org chemist to dump Elsevier. Tet Lett and Tetrahedron are not the journals they once were, and there’s plenty of quality competition. I’m not publishing there ever again. Opting out of ACS and RSC is a much bigger call. Who knows maybe BJOC will be the new JOC one day – and getting in early is a good thing.

    • Jan Jensen 8:04 pm on January 28, 2012 Permalink | Reply

      “My last two papers were in ACS journals because these were the most appropriate places for the students’ work”

      I have been thinking a bit about this lately. With journals like PLoS ONE and the fact that most people find articles through search engines, what do we as chemists mean by “appropriate journals”? Why not send everything to PLoS ONE? I don’t do this myself, but why not?

      The only fundamental issue that I see is the prestige factor. But once the paper is not in JACS or Nature Chemistry or 1-2 more, I don’t really see the any real gain in prestige. I am not an organic chemist, but is Inorg Chem and JOC really considered more prestigious than PLoS ONE? Or is it that most chemists think the latter is that new “like” button on Google? ;)

      • mattoddchem 8:21 am on January 29, 2012 Permalink | Reply

        Yes, it’s a nebulous idea “prestige”. I guess it comes down to where people i) trust, ii) browse and iii) are likely to publish, or have published, related work. For those last two papers from my group the journal had recently published related work, which we cited, meaning that those authors are likely to read our paper too. It sounds ludicrous when I say it, but it’s like a common area for a reading group. Before impact factors I think this was even more important – people would submit to the journal that had published the most relevant work recently. There is no need for this today. And yes, why not just submit everything to PLoS ONE? I don’t know.

        One of the things that bothers me about journal hierarchy is that it’s essentially a time-saver for the reader/assessor. If a paper is published in a certain journal we, as a reader, can form an opinion about the likely importance of the paper without having read it. Usually a paper in a top-tier journal has been refereed by 2-3 people. For something like Angewandte, I know from experience that a good report and a mediocre report is enough for a rejection. So let’s say two people will be responsible for a paper getting into a top-tier journal. Is the kind of reassurance we need about a paper’s quality? Have we not all read papers in big journals dealing with a very specialised area and thought “How did THAT get in?” because we are outside that field, perhaps? So we are relying on two people we don’t know, to judge something we are not familiar with and who may have very human political reasons for their decision, and yet we still somehow form a judgement of quality. It’s odd. Nevertheless the brand of certain journals provides us with an opinion of an individual paper. I suspect that will continue, because we as a species like labour-saving devices. So yes, some “top-tier” places will remain and thrive while other journals expand their efforts at article-level metrics and other devices for assessing an individual paper’s importance, rather than having to inductively judge that from an impact factor.

        • Jan Jensen 5:54 pm on January 29, 2012 Permalink | Reply

          I agree with you. But that’s top-tier journals like JACS and Angewandte. And I would submit that a CV filled with only such publications would be impressive.

          But what about the journals where *most* chemists publish *most* of their articles? JOC, J Phys Chem, etc? Do they really add more prestige to a CV than PLoS ONE? That’s one question I am struggling with. (The other is whether it is disingenuous to semi-boycott non-open access journals). Any thoughts?

          Imagining my publication list where all non-top tier publications have been published in PLoS ONE, I am left with another gut reaction: narrow research scope. Generally, publication in a diverse set of journals signals multidisciplinarity. However, this is a non-issue for PLoS ONE.

          • mattoddchem 9:23 pm on January 29, 2012 Permalink | Reply

            Sure, that’s what I was struggling to say. Devil take the hindmost – the top tier journals have the least to fear from open access, but time passes and times change. PLoS Biology/Medicine etc have huge impact factors. PLoS One’s impact factor is, I believe, higher than JOC’s at the moment. It’s a difficult transitional period for open access. Some new journals are coming along that might spur things along a bit. But it is still the case that panels looking at applicants scan paper lists for journals in order to save time – quite reasonable thing to do if there are 100 applicants for a job. I have no doubt this occurs when assessing people submitting grants, too – lower-ranked journals gives one a quick excuse to rate the grant badly. Now imagine we just had one journal. The articles would need to be assessed for importance, not the journal.

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